To reduce the development of drug-resistant bacteria and maintain
the effectiveness of AZACTAM® and other antibacterial
drugs, AZACTAM should be used only to treat or prevent infections that are
proven or strongly suspected to be caused by bacteria.

DESCRIPTION

AZACTAM® (aztreonam injection)
contains the active ingredient aztreonam, a monobactam. It was originally
isolated from Chromobacterium violaceum. It is a synthetic
bactericidal antibiotic.

The monobactams, having a unique monocyclic beta-lactam nucleus,
are structurally different from other beta-lactam antibiotics (eg, penicillins,
cephalosporins, cephamycins). The sulfonic acid substituent in the 1-position
of the ring activates the beta-lactam moiety; an aminothiazolyl oxime side
chain in the 3-position and a methyl group in the 4-position confer the specific
antibacterial spectrum and beta-lactamase stability.

AZACTAM (aztreonam injection) in the GALAXY plastic container (PL
2040) is a frozen, iso-osmotic, sterile, sodium-free, nonpyrogenic intravenous
solution. Each 50 mL of solution contains 1 g, or 2 g aztreonam with approximately
1.7 g, or 700 mg dextrose hydrous, USP added to adjust osmolality, and approximately
780 mg, or 1.6 g of arginine added for pH adjustment, respectively. Thawed
solutions have a pH in the range of 4.5 to 7.5. The solution is for intravenous
administration following thawing at room temperature or under refrigeration.

This GALAXY container is fabricated from a specially designed multilayer
plastic (PL 2040). Solutions are in contact with the polyethylene layer of
this container and can leach out certain chemical components of the plastic
in very small amounts within the expiration period. The suitability of the
plastic has been confirmed in tests in animals according to the USP biological
tests for plastic containers as well as by tissue culture toxicity studies.

Serum concentrations of aztreonam following completion of single
intravenous infusions of 500 mg, 1 g, and 2 g doses are depicted in Figure
1.

The serum levels of aztreonam following single 500 mg, 1 g or 2
g intravenous doses of AZACTAM (aztreonam injection) exceed the MIC90 for Neisseria sp., Haemophilus
influenzae and most genera of the Enterobacteriaceae for
8 hours (forEnterobacter sp., the 8-hour serum levels exceed
the MIC for 80% of strains). For Pseudomonas aeruginosa,
a single 2 g intravenous dose produces serum levels that exceed the MIC90 for
approximately 4 to 6 hours. All of the above doses of AZACTAM result in average
urine levels of aztreonam that exceed the MIC90 for
the same pathogens for up to 12 hours.

When aztreonam pharmacokinetics were assessed for adult and pediatric
patients, they were found to be comparable (down to 9 months old). The serum
half-life of aztreonam averaged 1.7 hours (1.5 to 2.0) in subjects with normal
renal function, independent of the dose. In healthy subjects, based on a 70
kg person, the serum clearance was 91 mL/min and renal clearance was 56 mL/min;
the apparent mean volume of distribution at steady-state averaged 12.6 liters,
approximately equivalent to extracellular fluid volume.

Average urine concentrations of aztreonam were approximately 1100µg/mL, 3500 µg/mL and 6600 µg/mL within the first 2 hours following
single 500 mg, 1 g and 2 g intravenous doses of AZACTAM (30-minute infusions),
respectively. The range of average concentrations for aztreonam in the 8-
to 12-hour urine specimens in these studies was 25 µg/mL to 120 µg/mL.
In healthy subjects, aztreonam is excreted in the urine about equally by active
tubular secretion and glomerular filtration. Approximately 60% to 70% of an
intravenous dose was recovered in the urine by 8 hours. Urinary excretion
of a single intravenous dose was essentially complete by 12 hours after injection.
About 12% of a single intravenous radiolabeled dose was recovered in the feces.
Unchanged aztreonam and the inactive beta-lactam ring hydrolysis product of
aztreonam were present in feces and urine.

Intravenous administration of a single 500 mg or 1 g dose of AZACTAM
every 8 hours for 7 days to healthy subjects produced no apparent accumulation
of aztreonam or modification of its disposition characteristics; serum protein
binding averaged 56% and was independent of dose.

Renal function was monitored in healthy subjects given aztreonam;
standard tests (serum creatinine, creatinine clearance, BUN, urinalysis and
total urinary protein excretion) as well as special tests (excretion of N-acetyl-β-glucosaminidase,
alanine aminopeptidase and β2-microglobulin)
were used. No abnormal results were obtained.

Aztreonam achieves measurable concentrations in the following body
fluids and tissues:

EXTRAVASCULAR CONCENTRATIONS OF AZTREONAM AFTER A SINGLE INTRAVENOUS
DOSE1

Fluid or Tissue

Dose(g)

Route

HoursPost-injection

NumberofPatients

MeanConcentration(µg/mL
or µg/g)

1Tissue penetration
is regarded as essential to therapeutic efficacy, but specific tissue levels
have not been correlated with specific therapeutic effects.

Fluids

bile

1

IV

2

10

39

blister
fluid

1

IV

1

6

20

bronchial
secretion

2

IV

4

7

5

cerebrospinal
fluid (inflamed
meninges)

2

IV

0.9-4.3

16

3

pericardial
fluid

2

IV

1

6

33

pleural
fluid

2

IV

1.1-3.0

3

51

synovial
fluid

2

IV

0.8-1.9

11

83

Tissues

atrial
appendage

2

IV

0.9-1.6

12

22

endometrium

2

IV

0.7-1.9

4

9

fallopian
tube

2

IV

0.7-1.9

8

12

fat

2

IV

1.3-2.0

10

5

femur

2

IV

1.0-2.1

15

16

gallbladder

2

IV

0.8-1.3

4

23

kidney

2

IV

2.4-5.6

5

67

large
intestine

2

IV

0.8-1.9

9

12

liver

2

IV

0.9-2.0

6

47

lung

2

IV

1.2-2.1

6

22

myometrium

2

IV

0.7-1.9

9

11

ovary

2

IV

0.7-1.9

7

13

skeletal
muscle

2

IV

0.3-0.7

6

16

skin

2

IV

0.0-1.0

8

25

sternum

2

IV

1

6

6

The concentration of aztreonam in saliva at 30 minutes after a
single 1 g intravenous dose (9 patients) was 0.2 µg/mL; in human milk
at 2 hours after a single 1 g intravenous dose (6 patients), 0.2 µg/mL;
in amniotic fluid at 6 to 8 hours after a single 1 g intravenous dose (5 patients),
2 µg/mL. The concentration of aztreonam in peritoneal fluid obtained
1 to 6 hours after multiple 2 g intravenous doses ranged between 12 µg/mL
and 90 µg/mL in 7 of 8 patients studied.

Concomitant administration of probenecid or furosemide and aztreonam
causes clinically insignificant increases in the serum levels of aztreonam.
Single-dose intravenous pharmacokinetic studies have not shown any significant
interaction between aztreonam and concomitantly administered gentamicin, nafcillin
sodium, cephradine, clindamycin or metronidazole. No reports of disulfiram-like
reactions with alcohol ingestion have been noted; this is not unexpected since
aztreonam does not contain a methyl-tetrazole side chain.

Microbiology

Aztreonam exhibits potent and specific activity in vitro against
a wide spectrum of gram-negative aerobic pathogens including Pseudomonas
aeruginosa. The bactericidal action of aztreonam results from the
inhibition of bacterial cell wall synthesis due to a high affinity of aztreonam
for penicillin binding protein 3 (PBP3). Aztreonam, unlike the majority of
beta-lactam antibiotics, does not induce beta-lactamase activity and its molecular
structure confers a high degree of resistance to hydrolysis by beta-lactamases
(ie, penicillinases and cephalosporinases) produced by most gram-negative
and gram-positive pathogens; it is, therefore, usually active against gram-negative
aerobic microorganisms that are resistant to antibiotics hydrolyzed by beta-lactamases.
It is active against many strains that are multiply-resistant to other antibiotics,
such as certain cephalosporins, penicillin, and aminoglycosides. Aztreonam
maintains its antimicrobial activity over a pH range of 6 to 8 in
vitro, as well as in the presence of human serum and under anaerobic
conditions.

Aztreonam has been shown to be active against most strains of the
following microorganisms, both in vitro and in clinical infections
as described in the INDICATIONS AND USAGE section.

The following in vitro data are available, but
their clinical significance is unknown.

Aztreonam exhibits in vitro minimal inhibitory
concentrations (MICs) of 8 µg/mL or less against most (≥90%) strains of the
following microorganisms; however, the safety and effectiveness of aztreonam
in treating clinical infections due to these microorganisms have not been
established in adequate and well-controlled clinical trials.

Aerobic gram-negative microorganisms:

Aeromonas hydrophila

Morganella morganii

Neisseria gonorrhoeae (including
penicillinase-producing strains)

Pasteurella multocida

Proteus vulgaris

Providencia stuartii

Providencia rettgeri

Yersinia enterocolitica

Aztreonam and aminoglycosides have been shown to be synergistic in
vitro against most strains of P. aeruginosa, many
strains of Enterobacteriaceae, and other gram-negative aerobic
bacilli.

Alterations of the anaerobic intestinal flora by broad spectrum
antibiotics may decrease colonization resistance, thus permitting overgrowth
of potential pathogens, eg, Candida and Clostridium species.
Aztreonam has little effect on the anaerobic intestinal microflora in in
vitro studies. Clostridium difficile and its cytotoxin
were not found in animal models following administration of aztreonam. (See ADVERSE REACTIONS: Gastrointestinal.)

Susceptibility Tests

Dilution Techniques: Quantitative
methods are used to determine antimicrobial minimal inhibitory concentrations
(MICs). These MICs provide estimates of the susceptibility of bacteria to
antimicrobial compounds. The MICs should be determined using a standardized
procedure. Standardized procedures are based on a dilution method5 (broth
or agar) or equivalent with standardized inoculum concentrations and standardized
concentrations of aztreonam powder. The MIC values should be interpreted according
to the following criteria:

b. The current absence of data on resistant strains
precludes defining any categories other than “Susceptible.” Strains yielding
MIC results suggestive of a “nonsusceptible” category should be submitted
to a reference laboratory for further testing.

For testing aerobic microorganisms other than Haemophilus
influenzae:

MIC (µg/mL)

Interpretation

≤8

Susceptible (S)

16

Intermediate (I)

≥32

Resistant (R)

When testing Haemophilus influenzaea:

MIC (µg/mL)

Interpretationb

≤2

Susceptible (S)

A report of “Susceptible” indicates that the pathogen is likely
to be inhibited if the antimicrobial compound in the blood reaches the concentrations
usually achievable. A report of “Intermediate” indicates that the result should
be considered equivocal, and, if the microorganism is not fully susceptible
to alternative, clinically feasible drugs, the test should be repeated. This
category implies possible clinical applicability in body sites where the drug
is physiologically concentrated or in situations where high dosage of drug
can be used. This category also provides a buffer zone which prevents small
uncontrolled technical factors from causing major discrepancies in interpretation.
A report of “Resistant” indicates that the pathogen is not likely to be inhibited
if the antimicrobial compound in the blood reaches the concentrations usually
achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of
laboratory control microorganisms to control the technical aspects of the
laboratory procedures. Standard aztreonam powder should provide the following
MIC values:

a. Range applicable only to tests performed by
broth microdilution method using Haemophilus Test Medium
(HTM).5

Microorganism

MIC (µg/mL)

Escherichia coli ATCC 25922

0.06-0.25

Haemophilus influenzaea ATCC
49247

0.12-0.5

Pseudomonas aeruginosa ATCC 27853

2.0-8.0

Diffusion Techniques: Quantitative
methods that require measurement of zone diameters also provide reproducible
estimates of the susceptibility of bacteria to antimicrobial compounds. One
such standardized procedure6 requires the use of
standardized inoculum concentrations. This procedure uses paper disks impregnated
with 30 µg aztreonam to test the susceptibility of microorganisms to aztreonam.

Reports from the laboratory providing results of the standard single-disk
susceptibility test with a 30 µg aztreonam disk should be interpreted according
to the following criteria:

b. The current absence of data on resistant strains
precludes defining any categories other than “Susceptible.” Strains yielding
zone diameter results suggestive of a “nonsusceptible” category should be
submitted to a reference laboratory for further testing.

For testing aerobic microorganisms other than Haemophilus
influenzae:

Zone diameter (mm)

Interpretation

≥22

Susceptible (S)

16 - 21

Intermediate (I)

≤15

Resistant (R)

When testing Haemophilus influenzaea:

Zone diameter (mm)

Interpretationb

≥26

Susceptible (S)

Interpretation should be as stated above for results using dilution
techniques. Interpretation involves correlation of the diameter obtained in
the disk test with the MIC for aztreonam.

As with standardized dilution techniques, diffusion methods require
the use of laboratory control microorganisms that are used to control the
technical aspects of the laboratory procedures. For the diffusion technique,
the 30 µg aztreonam disk should provide the following zone diameters in these
laboratory test quality control strains.

a. Range applicable only to tests performed by
disk diffusion method using Haemophilus Test Medium (HTM).6

Microorganism

Zone diameter (mm)

Escherichia coli ATCC 25922

28-36 mm

Haemophilus influenzaea ATCC
49247

30-38 mm

Pseudomonas aeruginosa ATCC 27853

23-29 mm

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain
the effectiveness of AZACTAM® and other antibacterial
drugs, AZACTAM should be used only to treat or prevent infections that are
proven or strongly suspected to be caused by susceptible bacteria. When culture
and susceptibility information are available, they should be considered in
selecting or modifying antibacterial therapy. In the absence of such data,
local epidemiology and susceptibility patterns may contribute to the empiric
selection of therapy.

AZACTAM (aztreonam injection) is indicated for the treatment of
the following infections caused by susceptible gram-negative microorganisms:

AZACTAM (aztreonam injection) is indicated for adjunctive therapy
to surgery in the management of infections caused by susceptible organisms,
including abscesses, infections complicating hollow viscus perforations, cutaneous
infections and infections of serous surfaces. AZACTAM is effective against
most of the commonly encountered gram-negative aerobic pathogens seen in general
surgery.

*Efficacy for this organism in this organ system was studied in
fewer than 10 infections.

Concurrent Therapy

Concurrent initial therapy with other antimicrobial agents and
AZACTAM is recommended before the causative organism(s) is known in seriously
ill patients who are also at risk of having an infection due to gram-positive
aerobic pathogens. If anaerobic organisms are also suspected as etiologic
agents, therapy should be initiated using an anti-anaerobic agent concurrently
with AZACTAM (see DOSAGE AND ADMINISTRATION).
Certain antibiotics (eg, cefoxitin, imipenem) may induce high levels of beta-lactamase in
vitro in some gram-negative aerobes such as Enterobacter and Pseudomonas species,
resulting in antagonism to many beta-lactam antibiotics including aztreonam.
These in vitro findings suggest that such beta-lactamase
inducing antibiotics not be used concurrently with aztreonam. Following identification
and susceptibility testing of the causative organism(s), appropriate antibiotic
therapy should be continued.

CONTRAINDICATIONS

This preparation is contraindicated in patients with known hypersensitivity
to aztreonam or any other component in the formulation.

WARNINGS

Both animal and human data suggest that AZACTAM is rarely cross-reactive
with other beta-lactam antibiotics and weakly immunogenic. Treatment with
aztreonam can result in hypersensitivity reactions in patients with or without
prior exposure. (See CONTRAINDICATIONS.)

Careful inquiry should be made to determine whether the patient
has any history of hypersensitivity reactions to any allergens.

While cross-reactivity of aztreonam with other beta-lactam antibiotics
is rare, this drug should be administered with caution to any patient with
a history of hypersensitivity to beta-lactams (eg, penicillins, cephalosporins,
and/or carbapenems). Treatment with aztreonam can result in hypersensitivity
reactions in patients with or without prior exposure to aztreonam. If an allergic
reaction to aztreonam occurs, discontinue the drug and institute supportive
treatment as appropriate (eg, maintenance of ventilation, pressor amines,antihistamines, corticosteroids). Serious hypersensitivity reactions may require
epinephrine and other emergency measures. (See ADVERSE
REACTIONS.)

Clostridium difficile associated diarrhea (CDAD)
has been reported with use of nearly all antibacterial agents, including AZACTAM,
and may range in severity from mild diarrhea to fatal colitis. Treatment with
antibacterial agents alters the normal flora of the colon leading to overgrowth
of C. difficile.

C. difficile produces toxins A and B which contribute
to the development of CDAD. Hypertoxin-producing strains of C. difficile cause
increased morbidity and mortality, as these infections can be refractory to
antimicrobial therapy and may require colectomy. CDAD must be considered in
all patients who present with diarrhea following antibiotic use. Careful medical
history is necessary since CDAD has been reported to occur over two months
after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed
against C. difficile may need to be discontinued. Appropriate
fluid and electrolyte management, protein supplementation, antibiotic treatment
of C. difficile, and surgical evaluation should be instituted
as clinically indicated.

PRECAUTIONS

General

Prescribing AZACTAM in the absence of a proven or strongly suspected
bacterial infection or a prophylactic indication is unlikely to provide benefit
to the patient and increases the risk of the development of drug-resistant
bacteria.

In patients with impaired hepatic or renal function, appropriate
monitoring is recommended during therapy.

If an aminoglycoside is used concurrently with aztreonam, especially
if high dosages of the former are used or if therapy is prolonged, renal function
should be monitored because of the potential nephrotoxicity and ototoxicity
of aminoglycoside antibiotics.

The use of antibiotics may promote the overgrowth of nonsusceptible
organisms, including gram-positive organisms (Staphylococcus aureus and Streptococcus
faecalis) and fungi. Should superinfection occur during therapy,
appropriate measures should be taken.

Information for Patients

Patients should be counseled that antibacterial drugs including
AZACTAM should only be used to treat bacterial infections. They do not treat
viral infections (eg, the common cold). When AZACTAM is prescribed to treat
a bacterial infection, patients should be told that although it is common
to feel better early in the course of therapy, the medication should be taken
exactly as directed. Skipping doses or not completing the full course of therapy
may (1) decrease the effectiveness of the immediate treatment and (2) increase
the likelihood that bacteria will develop resistance and will not be treatable
by AZACTAM or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually
ends when the antibiotic is discontinued. Sometimes after starting treatment
with antibiotics, patients can develop watery and bloody stools (with or without
stomach cramps and fever) even as late as two or more months after having
taken the last dose of the antibiotic. If this occurs, patients should contact
their physician as soon as possible.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies in animals have not been performed.

Genetic toxicology studies performed in vivo and in
vitro with aztreonam in several standard laboratory models revealed
no evidence of mutagenic potential at the chromosomal or gene level.

Two-generation reproduction studies in rats at daily doses up to
20 times the maximum recommended human dose, prior to and during gestation
and lactation, revealed no evidence of impaired fertility. There was a slightly
reduced survival rate during the lactation period in the offspring of rats
that received the highest dosage, but not in offspring of rats that received
five times the maximum recommended human dose.

Pregnancy

Pregnancy Category B

Aztreonam crosses the placenta and enters the fetal circulation.

Studies in pregnant rats and rabbits, with daily doses up to 15
and 5 times, respectively, the maximum recommended human dose, revealed no
evidence of embryo- or fetotoxicity or teratogenicity. No drug induced changes
were seen in any of the maternal, fetal, or neonatal parameters that were
monitored in rats receiving 15 times the maximum recommended human dose of
aztreonam during late gestation and lactation.

There are no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response,
aztreonam should be used during pregnancy only if clearly needed.

Nursing Mothers

Aztreonam is excreted in human milk in concentrations that are
less than 1% of concentrations determined in simultaneously obtained maternal
serum; consideration should be given to temporary discontinuation of nursing
and use of formula feedings.

Pediatric Use

The safety and effectiveness of intravenous AZACTAM have been established
in the age groups 9 months to 16 years. Use of AZACTAM in these age groups
is supported by evidence from adequate and well-controlled studies of AZACTAM
in adults with additional efficacy, safety, and pharmacokinetic data from
noncomparative clinical studies in pediatric patients. Sufficient data are
not available for pediatric patients under 9 months of age or for the following
treatment indications/pathogens: septicemia and skin and skin-structure infections
(where the skin infection is believed or known to be due to H. influenzae type
b). In pediatric patients with cystic fibrosis, higher doses of AZACTAM may
be warranted. (See CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION, and CLINICAL STUDIES.)

Geriatric Use

Clinical studies of AZACTAM did not include sufficient numbers
of subjects aged 65 years and over to determine whether they respond differently
from younger subjects. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients.7-10 In
general, dose selection for an elderly patient should be cautious, reflecting
the greater frequency of decreased hepatic, renal, or cardiac function, and
of concomitant disease or other drug therapy.

In elderly patients, the mean serum half-life of aztreonam increased
and the renal clearance decreased, consistent with the age-related decrease
in creatinine clearance.1-4 Since aztreonam is
known to be substantially excreted by the kidney, the risk of toxic reactions
to this drug may be greater in patients with impaired renal function. Because
elderly patients are more likely to have decreased renal function, renal function
should be monitored and dosage adjustments made accordingly (see DOSAGE AND ADMINISTRATION: Renal Impairment in Adult
Patients and Dosage in
the Elderly).

AZACTAM contains no sodium.

ADVERSE REACTIONS

Local reactions (eg, phlebitis/thrombophlebitis; discomfort/swelling)
following IV administration occurred at rates of approximately 1.9%.

Systemic reactions (considered to be related to therapy or of uncertain
etiology) occurring at an incidence of 1% to 1.3% include diarrhea, nausea
and/or vomiting, and rash. Reactions occurring at an incidence of less than
1% are listed within each body system in order of decreasing severity:

Gastrointestinal—abdominal cramps;
rare cases of C. difficile-associated diarrhea, including
pseudomembranous colitis, or gastrointestinal bleeding have been reported.
Onset of pseudomembranous colitis symptoms may occur during or after antibiotic
treatment. (See WARNINGS.)

Pediatric Adverse Reactions

Of the 612 pediatric patients who were treated with AZACTAM in
clinical trials, less than 1% required discontinuation of therapy due to adverse
events. The following systemic adverse events, regardless of drug relationship,
occurred in at least 1% of treated patients in domestic clinical trials: rash
(4.3%), diarrhea (1.4%), and fever (1.0%). These adverse events were comparable
to those observed in adult clinical trials.

In 343 pediatric patients receiving intravenous therapy, the following
local reactions were noted: pain (12%), erythema (2.9%), induration (0.9%),
and phlebitis (2.1%). In the US patient population, pain occurred in 1.5%
of patients, while each of the remaining three local reactions had an incidence
of 0.5%.

In US pediatric clinical trials, neutropenia (absolute neutrophil
count less than 1000/mm3) occurred in 11.3% of
patients (8/71) younger than 2 years receiving 30 mg/kg q6h. AST and ALT elevations
to greater than 3 times the upper limit of normal were noted in 15% to 20%
of patients aged 2 years or above receiving 50 mg/kg q6h. The increased frequency
of these reported laboratory adverse events may be due to either increased
severity of illness treated or higher doses of AZACTAM administered.

Adverse Laboratory Changes

Adverse laboratory changes without regard to drug relationship
that were reported during clinical trials were:

Hepatic—elevations of AST (SGOT), ALT (SGPT),
and alkaline phosphatase; signs or symptoms of hepatobiliary dysfunction occurred
in less than 1% of recipients (see above).

OVERDOSAGE

If necessary, aztreonam may be cleared from the serum by hemodialysis
and/or peritoneal dialysis.

DOSAGE AND ADMINISTRATION

Dosage in Adult Patients

AZACTAM (aztreonam injection), an intravenous solution in GALAXY
plastic containers (PL 2040), is intended for intravenous use only. Dosage
should be determined by susceptibility of the causative organisms, severity
and site of infection, and the condition of the patient.

The duration of therapy depends on the severity of infection. Generally,
AZACTAM should be continued for at least 48 hours after the patient becomes
asymptomatic or evidence of bacterial eradication has been obtained. Persistent
infections may require treatment for several weeks. Doses smaller than those
indicated should not be used.

Renal Impairment in Adult Patients

Prolonged serum levels of aztreonam may occur in patients with
transient or persistent renal insufficiency. Therefore, the dosage of AZACTAM
should be halved in patients with estimated creatinine clearances between
10 mL/min/1.73 m2 and 30 mL/min/1.73 m2 after
an initial loading dose of 1 g or 2 g.

When only the serum creatinine concentration is available, the
following formula (based on sex, weight, and age of the patient) may be used
to approximate the creatinine clearance (Clcr). The serum creatinine should
represent a steady state of renal function.

In patients with severe renal failure (creatinine clearance less
than 10 mL/min/1.73 m2), such as those supported
by hemodialysis, the usual dose of 500 mg, 1 g or 2 g should be given initially.
The maintenance dose should be one-fourth of the usual initial dose given
at the usual fixed interval of 6, 8 or 12 hours. For serious or life-threatening
infections, in addition to the maintenance doses, one-eighth of the initial
dose should be given after each hemodialysis session.

Dosage in the Elderly

Renal status is a major determinant of dosage in the elderly; these
patients in particular may have diminished renal function. Serum creatinine
may not be an accurate determinant of renal status. Therefore, as with all
antibiotics eliminated by the kidneys, estimates of creatinine clearance should
be obtained, and appropriate dosage modifications made if necessary.

Because of the serious nature of infections due to Pseudomonas
aeruginosa, dosage of 2 g every 6 or 8 hours is recommended, at least
upon initiation of therapy, in systemic infections caused by this organism
in adults.

CLINICAL STUDIES

A total of 612 pediatric patients aged 1 month to 12 years were
enrolled in uncontrolled clinical trials of aztreonam in the treatment of
serious gram-negative infections, including urinary tract, lower respiratory
tract, skin and skin-structure, and intra-abdominal infections.

Directions for Use of AZACTAM (aztreonam injection) in GALAXY Plastic Container (PL 2040).

AZACTAM (aztreonam injection) in GALAXY plastic container (PL 2040)
is to be administered as an intermittent intravenous infusion only.

Storage

Store in a freezer capable of maintaining a temperature of -20°
C (-4° F).

Thawing of Plastic Containers

Thaw frozen container at room temperature, 25° C (77°
F) or in a refrigerator, 2° to 8° C (36° to 46° F). After
thawing is complete, invert the container to assure a well-mixed solution. (DO
NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION.)

Check for minute leaks by squeezing container firmly. If leaks
are detected, discard solution as sterility may be impaired.

The container should be visually inspected. Thawed solutions should
not be used unless clear; solutions will be colorless to yellow. Components
of the solution may precipitate in the frozen state and will dissolve upon
reaching room temperature with little or no agitation. If after visual inspection
the solution remains discolored, cloudy, or if an insoluble precipitate is
noted or if any seals or outlet ports are not intact, the container should
be discarded.

DO NOT ADD SUPPLEMENTARY MEDICATION.

The thawed solution in GALAXY plastic container (PL 2040) remains
chemically stable for either 14 days under refrigeration (2° to 8°
C/36° to 46° F) or for 48 hours at room temperature (25° C/77°
F). DO NOT REFREEZE THAWED ANTIBIOTICS.

Preparation for Intravenous Administration (Use aseptic technique)

Additives or other medication should not be added to AZACTAM (aztreonam
injection) in GALAXY plastic container (PL 2040) or infused simultaneously
through the same intravenous line. If the same intravenous line is used for
sequential infusion of several different drugs, it should be flushed before
and after infusion of AZACTAM (aztreonam injection) in GALAXY plastic container
(PL 2040) with an infusion solution compatible with AZACTAM (aztreonam injection)
in GALAXY plastic container (PL 2040)* and any other drug(s) administered
via this common line.

It is recommended that the intravenous administration apparatus
be replaced at least once every 48 hours.

CAUTION: Do not use plastic containers in series connections.
Such use could result in an embolism due to residual air being drawn from
the primary container before administration of the fluid from the secondary
container is complete.

Intravenous Administration

Infusion of AZACTAM (aztreonam injection) in GALAXY plastic container
(PL 2040) should be completed within a 20- to 60-minute period. The plastic
container is a single-dose unit; discard any unused portion remaining in the
container.

AZACTAM® is a registeredtrademark of Bristol-Myers Squibb Company licensed exclusively in the US to
EPI.Galaxy, Dianeal, Plasma-Lyte, and Travert are registered trademarks
of Baxter International Inc.Ionosol® and
Normosol® are registered trademarks of Abbott
Laboratories Corporation.Isolyte® is
a registered trademark of McGaw Inc.